Cell-to-cell junctions are responsible for intercellular adhesion and the mediation of some forms of short range intercellular communication. We plan to examine the ultra-structure and function of cell-to-cell junctions in human epithelial tumors in an effort to determine if defects in junctions may explain some aspects of the behavior of human tumors. We plan to continue to examine tumors of the human urinary bladder tumors. Junctional frequency will be quantitated by morphometric techniques and their frequency will be correlated with tumor growth characteristics (i.e. extent of invasion and metastases). Junctional ultrastructure in tumors will be examined with high resolution thin-section and freeze-cleave electron microscopy techniques to determine the intramembranous organization of tumor cell junctions. We have determined that macula adherens junctions (desmosomes) are maldeveloped in tumors of the urinary bladder and will now examine zonula adherens, zonula occludens and nexus junctions for evidence of similar maldevelopment. Studies on urinary bladder tumors will be extended to other epithelial tumors, including skin tumors. Two-stage induction of epithelial carcinomas in animals may be explained, in part, by favored growth of cell variants in the cell population that are normally repressed by released from normal growth control by cocarcinogens (promoters). The mechanism of promotor action may involve modification of short range cell-to-cell interactions by disruption of cell junctions. We plan to examine the effects of cocarcinogens on cell junction structure.